Objective:To explore the clinicopathological characteristics and prognostic factors of bladder squamous cell carcinoma (SqCC)and bladder adenocarcinoma.Methods:A retrospective analysis of the clinical data of 107 patients with nonurothelial carcinoma of the bladder admitted to the First Affiliated Hospital of Zhengzhou University from October 2011 to January 2019 was performed. Among the 107 patients, 78 were males and 29 were females(ratio 2.69∶1), and the median age of onset was 62.0 years. According to histological types, patients were divided into SqCC group, urachal adenocarcinoma group and non-urachal adenocarcinoma group. There were 55 cases in the SqCC group, including 40 males and 15 females. Their mean age was 69.0(58.0, 75.0) years. 14 cases had the history of smoking. The clinic manifestation included hematuria in 35 cases, bladder irritation in 13 cases, dysuria in 2 cases and pain in 5 cases .Tumors located at the anterior and posterior walls in 18 cases, at the lateral wall in 27 cases, at the triangular area in 8 cases and at the apical wall in 2 cases. The average diameter of tumor was 4.5(3.0, 6.0) cm. 37 cases suffered with single tumor and 18 cases suffered with multiple tumors. The surgical method was radical cystectomy in 38 cases, partial cystectomy in 4 cases, TURBT in 9 cases, interventional surgery in 2 cases, and no operation in 2 cases. There were 20 cases in the urachal adenocarcinoma group, including 14 males and 6 females; age 53.5(43.5, 57.8) years; 6 cases with a history of smoking. The clinic manifestation included hematuria in 16 cases, bladder irritation in 1 case, pain in 2 cases and asymptomatic in 1 case. Tumors located at anterior and posterior walls in 4 cases and at apical wall in 16. The average diameter of tumor was 3.0(2.0, 4.8) cm. Single tumor was present in 18 cases, multiple tumors were present in 2 cases. The surgical method was partial cystectomy in 16 cases, radical cystectomy in 1 case, TURBT in 1 case and no operation in 2 cases. There were 32 cases in the non-urachal adenocarcinoma group, including 24 males and 8 females. Their mean age was 55.0(46.3, 70.8) years.11 cases had a history of smoking. The clinic manifestation included hematuria in 16 cases, bladder irritation in 3 cases, dysuria in one case and pain in 7 cases. Tumor located at anterior and posterior walls in 17 cases, at lateral wall in 7 cases, at triangular area in 5 cases and at apical wall in 3 cases. The average diameter of tumor was 3.6(2.0, 4.5) cm. 23 cases suffered with single tumor, 9 cases suffered with multiple tumors.The surgical method was radical cystectomy in 11 cases, partial cystectomy in 9 cases, TURBT in 9 cases , and no operation in 3 cases. The preoperative data of the three groups of tissue types were compared, the differences of age of onset, tumor diameter, tumor location, reason for treatment, operation method ( P<0.05)among the 3 groups were statistically significant. The clinicopathological characteristics and prognosis of the 3 groups of tissue types were compared, and the Cox proportional regression risk model was used to analyze the clinical factors affecting the prognosis. Results:91 patients were followed up, the overall follow-up rate was 85.1%, the median follow-up time was 26(7, 48) months. The 3-year and 5-year overall survival rates were 54.1% and 42.2%, respectively. In the SqCC group, 11 cases received chemotherapy; 3 cases received postoperative radiotherapy; 12 cases received postoperative perfusion.10 cases had recurrence; 17 cases had lymph node metastasis; 19 cases had distant metastasis; 5 cases were pT x in pT stage, 36 cases were pT 1-pT 2, 14 cases were pT 3-pT 4. 19 cases had unknown tumor differentiation, 4 cases had well differentiated, 24 cases had moderately differentiated and 8 cases had poorly differentiated. In the urachal adenocarcinoma group, 7 cases received chemotherapy, 3 cases had recurrence, 2 cases had lymph node metastasis, 2 cases had distant metastasis; 1 case was pT x in pT stage, 16 cases were pT 1-pT 2, 3 cases were pT 3-pT 4. 9 cases had unknown tumor differentiation, 3 cases had well differentiated, and 5 cases had moderately differentiated, 3 cases had poorly differentiated. In the urachal adenocarcinoma group, 3 cases received chemotherapy, 1 case received postradiotherapy, 11 cases received postoperative perfusion; 10 cases had recurrence. 5 cases had lymph node metastasis, 4 cases had distant metastasis, 6 cases were pT x, 21 cases were pT 1-pT 2 and 5 cases were pT 3-pT 4. 14 cases had unknown tumor differentiation, 8 cases had moderately differentiated and 10 cases had poorly differentiated.The postoperative general data of the three groups of tissue types were compared. There was statistically significant difference between whether there was postoperative perfusion and whether there was distant metastasis (all P<0.05). The univariate analysis results showed gender, age, surgical method, lymph node metastasis, distant metastasis, pT staging, tumor differentiation and histological type were risk factors that affect the prognosis(all P<0.05). Cox multivariate analysis showed that women ( HR=2.604, P=0.032) and distant metastases ( HR=2.571, P=0.026) were independent risk factors affecting the prognosis of patients. Conclusions:SqCC and adenocarcinoma are clinically rare and have poor prognosis. They often present with hematuria. Surgical treatment is the first choice. Radical cystectomy is the first choice for SqCC and non-urachal adenocarcinoma, and extended partial cystectomy is the first choice for urachal adenocarcinoma. Female and distant metastasis are independent risk factors affecting the prognosis of patients.

Laboratory evolution is an important approach to improve the performance of microorganisms. In the past decades, the methods for laboratory evolution have developed rapidly and applied widely. However, the commonly used evolution strategies for strains or specific proteins cannot achieve continuous mutation, and require multiple rounds of operation, therefore they are considered as a labor intensive process. The development of mutation and screening technologies have facilitated the development of continuous evolution in vivo and greatly improved the efficiency of laboratory evolution. The continuous in vivo evolution achieves in vivo mutation, perfectly combining mutation with screening to evolve a specific phenotype with minimal human intervention. This review summarizes the recent advances of in vivo continuous evolution technologies for either genome-scale mutation or evolution of specific proteins. The principles of these technologies and their applications are introduced. On this basis, the advantages and limitations of these technologies are discussed. We also give a perspective of future development of continuous in vivo evolution.
Directed Molecular Evolution ; Humans ; Mutation ; Phenotype ; Proteins